Akt-mediated regulation of autophagy and tumorigenesis through Beclin 1 phosphorylation

Richard C. Wang, Yongjie Wei, Zhenyi An, Zhongju Zou, Guanghua Xiao, Govind Bhagat, Michael White, Julia Reichelt, Beth Levine

Research output: Contribution to journalArticle

403 Scopus citations

Abstract

Aberrant signaling through the class I phosphatidylinositol 3-kinase (PI3K)-Akt axis is frequent in human cancer. Here, we show that Beclin 1, an essential autophagy and tumor suppressor protein, is a target of the protein kinase Akt. Expression of a Beclin 1 mutant resistant to Akt-mediated phosphorylation increased autophagy, reduced anchorage-independent growth, and inhibited Akt-driven tumorigenesis. Akt-mediated phosphorylation of Beclin 1 enhanced its interactions with 14-3-3 and vimentin intermediate filament proteins, and vimentin depletion increased autophagy and inhibited Akt-driven transformation. Thus, Akt-mediated phosphorylation of Beclin 1 functions in autophagy inhibition, oncogenesis, and the formation of an autophagy-inhibitory Beclin 1/14-3-3/vimentin intermediate filament complex. These findings have broad implications for understanding the role of Akt signaling and intermediate filament proteins in autophagy and cancer.

Original languageEnglish (US)
Pages (from-to)956-959
Number of pages4
JournalScience
Volume338
Issue number6109
DOIs
StatePublished - Nov 16 2012

ASJC Scopus subject areas

  • General

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